Effectiveness of Exercise Intervention in Preventing Active Arthritis Exacerbation in an SKG Mouse Model of Rheumatoid Arthritis

Ozone, K.; Kumagai, T.; Arakawa, K.; Sugasawa, T.; Gu, W.; Kawabata, S.; Shimada, N.; Takahashi, H.; Yoneno, M.; Minegishi, Y.; Takahata, K.; Sato, M.; Oka, Y.; Kanemura, N.

doi:10.1101/2024.08.25.609287

bioRxiv · 10.1101/2024.08.25.609287

Effectiveness of Exercise Intervention in Preventing Active Arthritis Exacerbation in an SKG Mouse Model of Rheumatoid Arthritis

Ozone, K.·Kumagai, T.·Arakawa, K.·Sugasawa, T.·Gu, W.·Kawabata, S.·Shimada, N.·Takahashi, H.·Yoneno, M.·Minegishi, Y.·Takahata, K.·Sato, M.·Oka, Y.·Kanemura, N.

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Abstract

ObjectivesTo investigate the effects of low-intensity exercise on active arthritis in an SKG mouse model of human rheumatoid arthritis (RA) pathology. MethodsTwenty-four female SKG mice were divided into three groups: sedentary (control), AR (induced arthritis), and AREx (induced arthritis plus low-intensity exercise). Arthritis was induced via intraperitoneal administration of mannan. After a 2-week inflammation period, low-intensity treadmill exercise was performed only in the AREx group. Arthritis was assessed weekly during the rearing period. After 4 weeks of exercise, histological and bone morphometric analyses of the right ankle joint were performed. A histological analysis of the gastrocnemius muscle was also performed. Bulk mRNA sequencing was conducted on the left synovial membrane-fat pad (SM-FP) complex. ResultsThe synovitis score showed no change; however, the arthritis score was significantly lower in the AREx group than in the AR group (p<0.05), indicating that low-intensity exercise suppressed arthritis exacerbation. The calcaneal and talar bone volumes decreased in the AR group, whereas the AREx group showed no significant change. In the SM-FP complex tissue, the gene expression of inflammatory cytokines decreased in the AREx group compared with the AR group, particularly the suppression of IL6/Jak/Stat3. Immunohistochemical analysis revealed significantly decreased expression of pro-inflammatory cytokines and increased expression of anti-inflammatory cytokines in the synovium of the AREx group compared with the AR group (p<0.05). ConclusionLow-intensity exercise therapy for active RA showed anti-inflammatory and suppressive effects on arthritis exacerbation in SKG mice, a mouse model of human RA pathology. Key messagesO_LIExercise had an anti-inflammatory effect on SKG mice, a mouse model of rheumatoid arthritis. C_LIO_LIExercise suppresses pro-inflammatory cytokine pathways such as IL6/Jak/Stat3 signalling in the synovial-fat complex tissue. C_LIO_LIExercise therapy is effective in improving the pathophysiology of active rheumatoid arthritis. C_LI

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Ozone, K., Kumagai, T., Arakawa, K., Sugasawa, T., Gu, W., Kawabata, S., Shimada, N., Takahashi, H., Yoneno, M., Minegishi, Y., Takahata, K., Sato, M., Oka, Y., Kanemura, N.. 2024-08-25. Effectiveness of Exercise Intervention in Preventing Active Arthritis Exacerbation in an SKG Mouse Model of Rheumatoid Arthritis. https://doi.org/10.1101/2024.08.25.609287

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